Published online before print June 13, 2002, 10.1148/radiol.2242010982
(Radiology 2002;224:379-382.)
© RSNA, 2002
Nonvisualization of the Fetal Gallbladder in Early Pregnancy: Comparison with Clinical Outcome1
Shraga Blazer, MD,
Etan Z. Zimmer, MD and
Moshe Bronshtein, MD
1 From the Departments of Neonatology (S.B.) and Obstetrics and Gynecology (E.Z.Z., M.B.), Rambam Medical Center and Faculty of Medicine, Technion-Israel Institute of Technology, 8 Ha’Aliyah St, Haifa 35254, Israel. Received May 30, 2001; revision requested July 10; revision received October 30; accepted December 12. Address correspondence to S.B. (e-mail: blazer@rambam.health.gov.il).
 |
ABSTRACT
|
|---|
PURPOSE: To prospectively assess the frequency of a nonvisualized fetal gallbladder in early pregnancy and to determine its prognostic value.
MATERIALS AND METHODS: Fetal transvaginal ultrasonography (US) was performed in 29,749 consecutive pregnant women at 14–16 weeks gestation. A nonvisualized fetal gallbladder was defined if the gallbladder could not be depicted during two targeted examinations within 1 week. In such cases, women were offered an amniocentesis for fetal karyotype and hepatic enzyme analysis. Repeat transabdominal fetal US was performed at 22–26 weeks’ gestation. If the gallbladder was still not depicted, US was performed postnatally.
RESULTS: The gallbladder was not visualized in early pregnancy in 34 fetuses (0.1%; incidence of one in 875 pregnancies). Associated structural malformations were detected in 14 of 34 (41%) fetuses, five of which also had an abnormal karyotype. Pregnancy was terminated in nine of these 14 fetuses. In the remaining five patients who continued pregnancy, the gallbladder was detected later in pregnancy in four. However, only one infant was healthy. Nonvisualization of the gallbladder as an isolated finding was noted in 20 of 34 (59%) fetuses, all of which had a normal outcome. The gallbladder was detected later in pregnancy in 11 of these fetuses and after birth in two neonates, while no gallbladder was detected after delivery in five other neonates. Two patients were lost to follow-up.
CONCLUSION: Nonvisualization of the fetal gallbladder in early pregnancy is uncommon but associated in many cases with other fetal anomalies.
© RSNA, 2002
Index terms: Fetus, abnormalities, 856.876 • Fetus, growth and development, 856.876 • Gallbladder, abnormalities, 856.876 • Pregnancy, abnormalities, 856.876
|
INTRODUCTION
|
|---|
A search for the gallbladder is an integral part of a detailed fetal ultrasonographic (US) examination. Some investigators have found that the inability to visualize the gallbladder may indicate fetal anomalies (1–4). Other investigators, however, have reported a high rate of nonvisualization of the gallbladder in fetuses with normal outcomes (5). The aims of this prospective study were to assess the frequency of a nonvisualized fetal gallbladder in early pregnancy and to determine its prognostic value.
|
MATERIALS AND METHODS
|
|---|
In this prospective study, which was conducted during a 10-year period, 29,749 consecutive pregnant women were scanned at 14–16 weeks gestation. The study was approved by the Helsinki Committee of Rambam Medical Center in Haifa, Israel, and informed consent was obtained from all women. The study population consisted of self-referred patients who were interested in early US detection of fetal anomalies or patients who were referred by their physicians for the same purpose or for a second opinion. This large series reflects the tendency to perform a detailed targeted US examination on almost every pregnant woman in our practice area. The examination at 14–16 weeks gestation is performed by means of transvaginal US. Additional transabdominal US is sometimes needed in cases in which an insufficient image is obtained with the transvaginal method.
Eighty-seven percent of the women had low risk for fetal anomalies and hereditary or congenital syndromes, while 13% had increased risk as a result of exposure to medications or ionizing radiation, family history of congenital malformations, or consanguinity. All examinations were performed by the same sonologist (M.B.) by using an ESI 3,000 machine (Elscint, Haifa, Israel) with a 7.5-MHz annular-array vaginal transducer and 3.5- and 5.0-MHz abdominal probes. Color Doppler US was not performed.
The gallbladder usually appears as a small, hypoechoic, oval or rectangular cystlike structure located to the right of the intrahepatic umbilical vein. It is usually located at the lower border of the liver, close to the intestinal loops (Figure). A careful search for the gallbladder was performed whenever it was not depicted in its normal place. To discount the possibility that the gallbladder was not detected because of technical problems, a nonvisualized fetal gallbladder was defined when the gallbladder could not be depicted during two 30-minute targeted US examinations within a 1-week period.
View larger version (159K):
[in this window]
[in a new window]
[Download PPT slide]
|
US images show the fetal gallbladder in four fetuses at 15-16 weeks’ gestation. A,B, Parasagittal views of the gallbladder (arrows). The gallbladder is located between the liver and the intestine. C,D, Transverse oblique views of the gallbladder (arrows). The gallbladder is located near the intrahepatic umbilical vein (v) on the right side and at the same level as the stomach (s) on the left side.
|
|
In all patients in whom the gallbladder was not detected, the option of amniocentesis was offered to the parents. A search for cystic fibrosis, hepatic enzyme tests, and chromosomal analyses were performed. Furthermore, all patients who continued the pregnancy underwent repeat transabdominal US at 22–26 weeks’ gestation to reevaluate the fetal anatomy and to search again for the fetal gallbladder. Some patients decided to undergo an extra US examination between the 26th week and delivery. A postnatal US search for the gallbladder was performed in all neonates in whom a gallbladder had not been seen in utero, and the outcome of each pregnancy was noted. Postnatal US was performed by sonologists in the hospitals in which the neonates were born. All neonates underwent US in the first 72 hours of life. At least 4 hours after feeding, a search for the gallbladder was performed with different US planes in the right upper abdominal quadrant, subcostal area, and hepatic region. In neonates in whom the gallbladder was not detected, repeat US was performed at the age of 1 year. The medical records of the fetuses and neonates with a nonvisualized gallbladder during pregnancy were reviewed by the authors, and all medical and developmental problems were considered.
|
RESULTS
|
|---|
Among the 29,749 pregnancies included in the study, the gallbladder was not visualized in 34 fetuses at 14–16 weeks’ gestation, an incidence of one in 875 (0.1%) pregnancies. In three additional pregnancies, the previously nonvisualized fetal gallbladder was detected at a second US examination within a 1-week period. All three of these fetuses had a normal outcome. Of the 34 fetuses with a nonvisualized gallbladder, 14 fetuses had associated US anomalies, and 20 fetuses had nonvisualization of the gallbladder as an isolated finding (Tables 1, 2).
View this table:
[in this window]
[in a new window]
|
TABLE 1. Outcome of 20 Fetuses with Nonvisualization of the Gallbladder in Early Pregnancy as an Isolated Finding
|
|
View this table:
[in this window]
[in a new window]
|
TABLE 2. Outcome of 14 Fetuses with Nonvisualization of the Gallbladder and Additional US Findings in Early Pregnancy
|
|
All 20 fetuses with a nonvisualized gallbladder as an isolated finding had a normal karyotype. Of these 20 fetuses, there were 13 in which the gallbladder was detected later in pregnancy or after birth (Table 1). In five other fetuses, the gallbladder could not be depicted during pregnancy nor after birth; all these infants were healthy. Two patients in whom the gallbladder was not detected during pregnancy were lost to follow-up.
Of the 14 fetuses with associated structural anomalies, five also had a chromosomal abnormality (Table 2). Of these five fetuses, pregnancy was terminated in four with triploidy. Because of the destructive nature of the procedure, it was not possible to confirm the absence of the gallbladder at postmortem examination. In the single fetus with XYY karyotype, the parents decided to continue the pregnancy, and the gallbladder was detected at 26 weeks’ gestation.
There were nine fetuses with associated structural anomalies but a normal karyotype (Table 2). In three of these fetuses, the gallbladder was detected later in pregnancy. Pregnancy was terminated in five patients. Postmortem examination was performed on the two fetuses with cystic fibrosis, and a small dysplastic or rudimentary gallbladder was depicted. A small hypoplastic gallbladder was also found in a neonate with Potter syndrome (Table 2).
The carrier state for cystic fibrosis was evaluated in all pregnancies except two with associated anomalies (one with bilateral renal agenesis and one with nonimmune hydrops fetalis). Cystic fibrosis was diagnosed in two fetuses (Table 2).
Hepatic enzymes were available for analysis in 18 fetuses, 14 from the group with an isolated finding of a nonvisualized gallbladder and four from the group with an additional US finding. Except for one fetus with XYY karyotype, all of the other fetuses in which hepatic enzymes were evaluated had a normal karyotype. An abnormal enzyme level (below the first percentile) was observed in only one fetus with cystic fibrosis. Of note, there was another fetus with cystic fibrosis in which hepatic enzymes were not evaluated.
Overall, there were 34 fetuses in our study with a nonvisualized gallbladder in early pregnancy. Nine of these pregnancies were terminated, and 25 pregnancies were continued. Of the 25 patients in whom pregnancies were continued, 23 were available for follow-up. The gallbladder was detected later during pregnancy or after birth in 17 of these patients.
|
DISCUSSION
|
|---|
This study shows a gallbladder detection rate of 99.9% at 14–16 weeks’ gestation. Our results contrast with those of Hertzberg et al (5), who failed to visualize the gallbladder in 68.6% of fetuses at 12–16 weeks’ gestation, in 23.3% at 16–20 weeks’ gestation, and in 7.1% at 20–24 weeks’ gestation. The discrepancy in the incidence of gallbladder visualization between the two studies may depend on the US technique used. In our study, at 14–16 weeks’ gestation, all US was performed by using the transvaginal approach, while Hertzberg et al (5) performed transabdominal US in early pregnancy.
Results of previous studies have shown that the dimensions of the gallbladder increase until 30–36 weeks’ gestation, after which a plateau is observed (2,5). Regarding nonvisualization of the gallbladder during short time intervals, Goldstein et al (3) found that gallbladder dimensions remained almost constant during 3-hour intervals. Jouppila et al (6) showed that the fetal gallbladder volume did not decrease significantly in response to maternal glucose loading. These data may indicate that no significant changes of fetal gallbladder dimensions are expected during short time intervals. Hence, nonvisualization of the gallbladder is unusual and merits attention. This is in agreement with our finding that the gallbladder was detected at repeat US examination within 1 week in only three fetuses at 14–16 weeks’ gestation. These three fetuses were regarded as having a visualized gallbladder in early pregnancy.
Initially, the gallbladder is a solid mass at 4 weeks of embryonic life, and a definitive lumen develops by means of recanalization of the epithelium at the 7th week. Bile is formed by the liver at approximately 12 weeks’ gestation, entering the gallbladder and the intestinal system. When this fails to occur, the gallbladder remains atretic and does not develop (7).
In the 23 patients in whom pregnancies were continued and patients were available for follow-up, the gallbladder was detected later in pregnancy or after birth in 17 patients. In patients in whom the gallbladder was not visualized during the first examination, we performed additional 30-minute targeted US within 1 week to exclude the possibility of a technical problem in the visualization of the gallbladder. As noted, we did not visualize the gallbladder in 34 fetuses. It is speculated, therefore, that the gallbladder was not observed originally in these fetuses as a result of a late recanalization process of the gallbladder epithelium, which creates the hollow appearance.
Nonvisualization of the gallbladder in early pregnancy was associated with an alarming set of anomalies in 14 of 34 (41%) patients. This may indicate that absence or late development of the gallbladder is likely to be a part of other malformation syndromes. The findings of trisomy 18 and 21 syndromes in patients with a hypoplastic gallbladder have been previously described (5,8). In our series, we found five (17%) fetuses with chromosomal aberrations: one with trisomy XYY and four with triploidy. To the best of our knowledge, these aberrations have not been previously reported in association with nonvisualization of the gallbladder in early pregnancy. The relationship between aneuploidy and the gallbladder is difficult to explain; in fact, aneuploidy has been reported in fetuses with cholecystomegaly (8,9).
Cystic fibrosis is associated with small gallbladder volume in neonates (10). Duchatel et al (4) could not visualize the gallbladder in nine of 12 fetuses with cystic fibrosis at 17–19 weeks’ gestation. In our two fetuses with cystic fibrosis and a nonvisualized gallbladder, autopsy revealed rudimentary and dysplastic gallbladders.
Agenesis of the gallbladder is a rare but well-known condition. Since the description of agenesis of the gallbladder by Bergman in 1701 (11), only 413 cases have been reported up to 1999 (12). The exact incidence of agenesis of the gallbladder is unknown, mainly because the estimated incidence has been calculated from reviews of case reports (13). In our series, the gallbladder was not detected during pregnancy or in the neonatal period in five healthy neonates. These cases may represent a benign variant of agenesis of the gallbladder. According to our data, the incidence of this anatomic variant is about one in 6,000 pregnancies. However, nonvisualization of the gallbladder may also be a marker of external biliary atresia, a rare anomaly that was not detected in our series. This anomaly might be excluded by evaluating the amniotic fluid for hepatic enzymes. Some investigators suggested that agenesis of the gallbladder may represent a congenital developmental defect of genetic origin (14–16). Therefore, if the fetal gallbladder cannot be observed, parental US examination should be considered. If no gallbladder is detected in either of the asymptomatic parents, this may be reassuring (17).
In summary, results of the present study show that the gallbladder can be observed in almost all fetuses in early pregnancy. Nonvisualization of the gallbladder in early pregnancy deserves special attention, since almost 40% of these fetuses have associated anomalies. It may also be a marker of cystic fibrosis or external biliary atresia. However, nonvisualization of the gallbladder, especially in fetuses in which this phenomenon is a solitary finding, may be associated with a normal outcome. Furthermore, in some cases it will be possible to depict the gallbladder later during pregnancy or after birth. Follow-up of all fetuses is recommended, and appropriate fetal examinations should be considered.
|
ACKNOWLEDGMENTS
|
|---|
The authors thank M. Perlmutter, BA, for her assistance in the preparation of the manuscript.
|
FOOTNOTES
|
|---|
Author contributions: Guarantors of integrity of entire study, S.B., E.Z.Z., M.B.; study concepts and design, S.B., E.Z.Z., M.B.; literature research, S.B., E.Z.Z., M.B.; clinical studies, S.B., E.Z.Z., M.B.; data acquisition, M.B.; data analysis/interpretation, S.B., E.Z.Z., M.B.; manuscript preparation, definition of intellectual content, editing, revision/review, and final version approval, S.B., E.Z.Z., M.B.
|
REFERENCES
|
|---|
- Bronshtein M, Weiner Z, Abramovici H, Filmar S, Erlik Y, Blumenfeld Z. Prenatal diagnosis of gallbladder anomalies: report of 17 cases. Prenat Diagn 1993; 13:851-861.[Medline]
- Chan L, Rao BK, Jiang Y, Endicott B, Wapner RJ, Reece EA. Fetal gallbladder growth and development during gestation. J Ultrasound Med 1995; 14:421-425.[Abstract]
- Goldstein I, Tamir A, Weisman A, Jakobi P, Copel JA. Growth of the fetal gallbladder in normal pregnancies. Ultrasound Obstet Gynecol 1994; 4:289-293.[CrossRef][Medline]
- Duchatel F, Muller F, Oury JF, Mennesson B, Boue J, Boue A. Prenatal diagnosis of cystic fibrosis: ultrasonography of the gallbladder at 17–19 weeks of gestation. Fetal Diagn Ther 1993; 8:28-36.
- Hertzberg BS, Kliewer MA, Maynor C, et al. Nonvisualization of the fetal gallbladder: frequency and prognostic importance. Radiology 1996; 199:679-682.[Abstract/Free Full Text]
- Jouppila P, Heikkinen J, Kirkinen P. Contractility of maternal and fetal gallbladder: an ultrasonographic study. J Clin Ultrasound 1985; 13:461-464.[Medline]
- Sadler TW. Digestive system. In: Sadler TW, eds. Langman’s medical embryology. 5th ed. Baltimore, Md: Williams & Wilkins, 1985; 224-246.
- Jones KL. Chromosomal abnormality syndromes. In: Jones KL, eds. Smith’s recognizable pattern of human malformations. 5th ed. Philadelphia, Pa: Saunders, 1997; 8-87.
- Sepulveda W, Nicolaidis P, Hollingsworth J, Fisk NM. Fetal cholecystomegaly: a prenatal marker of aneuploidy. Prenat Diagn 1995; 15:193-197.[Medline]
- Abramson SJ, Baker DH, Amodio JB, Berdon WE. Gastrointestinal manifestations of cystic fibrosis. Semin Roentgenol 1987; 22:97-113.[CrossRef][Medline]
- Bower JO. Congenital absence of the gall bladder. Ann Surg 1928; 88:80-90.[Medline]
- Singh B, Satyapal KS, Moodley J, Haffejee AA. Congenital absence of the gall bladder. Surg Radiol Anat 1999; 21:221-224.[Medline]
- Frey C, Bizer L, Ernst C. Agenesis of the gallbladder. Am J Surg 1967; 114:917-926.[CrossRef][Medline]
- Nadeau LA, Cloutier WA, Konecki JT, Morin G, Taylor RW. Hereditary gallbladder agenesis: twelve cases in the same family. J Maine Med Assoc 1972; 63:1-4.[Medline]
- Sterchi JM, Baine RW, Myers RT. Agenesis of the gallbladder: an inherited defect? South Med J 1977; 70:498-499.[Medline]
- Wilson JE, Deitrick JE. Agenesis of the gallbladder: case report and familial investigation. Surgery 1986; 99:106-109.[Medline]
- Bronshtein M, Zimmer EZ, Blazer S. Imaging studies of parents of fetuses with sonographic anomalies of uncertain prognosis. JAMA 2001; 285:737-738.[Free Full Text]
TOP
ABSTRACT
INTRODUCTION
